HLA class II susceptibility to multiple sclerosis among Ashkenazi and non-Ashkenazi Jews

Objective: To look for HLA class II alleles and haplo-types conferring susc eptibility to multiple sclerosis (MS) in the Jewish population of Israel. Design: Population-based cohort of clinically definite patients with MS tes ted prospectively over 7 years. Setting: Referral center in a neurology clinic at a university hospital in the greater Jerusalem area in Israel. Patients: A total of 162 consecutive patients with clinically definite MS f rom the 2 main ethnic Jewish groups in Israel: 104 Ashkenazi (80 with a rel apsing remitting or secondary progressive and 24 with a primary chronic pro gressive course of the disease) and 58 non-Ashkenazi (36 with a relapsing r emitting or secondary progressive course and 22 with a primary chronic prog ressive course of the disease), matched with 132 Ashkenazi and 120 non-Ashk enazi healthy controls. Main Outcome Measures: The relationship between the various HLA class II al leles and haplotypes and MS, as defined by the polymerase chain reaction an d sequence-specific oligonucleotide probe hybridization, among the Ashkenaz i and the non-Ashkenazi Jewish sections and with respect to the different c linical courses of the disease. Results: The haplotype DRB1*1501, DQA1*0102, DQB1*0602 was found to be asso ciated with MS among both Ashkenazi and non-Ashkenazi patients (P < .001 an d P = .04, respectively). Among the non-Ashkenazi patients, a new associati on of haplotypes DRB1*1303, DQA1*05, and DQB1*0301 with MS was detected (P = .03). The MS susceptibility alleles, DRB1*1501, DQA1*0102, and DQB1*0602, were found in association with the Ashkenazi patients (P < .001, P = .02, a nd P = .01, respectively); DRB1*1501 and DRB1*1303 were more frequently obs erved among the non-Ashkenazi patients (P = .03, P = .04, respectively). On subdivision of the patients into clinical subgroups, associations of DRB1* 0801, DQA1*0102, DQA1*0401, and DQB1*0602 with primary chronic progressive MS among the Ashkenazi patients were evident (P = .03, P = .04, P = .04 and P = .05, respectively), whereas DRB1*1501, DRB1*03011, and DQBI*0602 were associated with relapsing remitting or secondary progressive among the non- Ashkenazi patients (P = .05, P = .05, and P = .03, respectively). Conclusions: This study, unlike previous ones, is the first to show a signi ficant association between HLA class II alleles and MS in the Jewish popula tion. The association with the HLA-DR2-related haplotype is similar to that among non-Jewish white patients viith MS. Moreover, our data support the p ossibility that DRB1*1501 is the susceptibility allele responsible for the association between this haplotype and MS in the Jewish population. Our stu dy also underscores differences in HLA profiles between Ashkenazi and non-A shkenazi patients, and between the different clinical courses of the diseas e. The latter may indicate that the clinical courses of MS are influenced b y the genetic background.